Abstract: FR-PO0209
Dual Inhibition of PDGF-B and PDGF-D Attenuates Renal Fibrosis and Preserves Kidney Function in CKD Models
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 2
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Kanamori, Masakazu, Chugai Pharmabody Research Pte. Ltd., Singapore, Singapore
- Tsuboi, Yoshinori, Chugai Pharmaceutical Co., Ltd., Yokohama, Japan
- Yang, Beverly, Chugai Pharmabody Research Pte. Ltd., Singapore, Singapore
- Teranishi-Ikawa, Yuri, Chugai Pharmaceutical Co., Ltd., Yokohama, Japan
- Nambu, Takeru, Chugai Pharmaceutical Co., Ltd., Yokohama, Japan
- Murai, Atsuko, Chugai Pharmaceutical Co., Ltd., Yokohama, Japan
- Shimada, Hideaki, Chugai Pharmaceutical Co., Ltd., Yokohama, Japan
Background
Chronic kidney disease (CKD) progression is driven by mesenchymal cell activation, including fibroblast and mesangial cell proliferation, leading to renal fibrosis and functional decline. Platelet-derived growth factor (PDGF) signalling plays a central role in these processes; however, direct targeting of PDGF ligands or receptors has not been extensively pursued in clinical development for CKD, underscoring the need for alternative pathway inhibition strategies.
Methods
We developed PHEN09, a bispecific antibody designed to simultaneously neutralize PDGF-B and PDGF-D. Mechanistic activity was evaluated in human fibroblasts and renal mesangial cells by measuring PDGFRβ phosphorylation and proliferative responses. In vivo efficacy was assessed across multiple preclinical kidney disease models, including a unilateral ureteral obstruction (UUO) mouse model, a Thy-1–induced mesangial proliferative rat model, and Col4a3 knockout mice as a model of progressive CKD.
Results
PHEN09 potently inhibited PDGF-B- and PDGF-D-mediated PDGFRβ activation and cell proliferation in vitro. In vivo, PHEN09 significantly attenuated renal interstitial fibrosis in the UUO mouse model and suppressed mesangial proliferation in the Thy-1 nephritis rat model. In Col4a3 knockout mice, PHEN09 reduced glomerulosclerosis and interstitial fibrosis and significantly preserved renal function.
Conclusion
Simultaneous ligand-level blockade of PDGF-B and PDGF-D by the bispecific antibody PHEN09 effectively suppresses pathogenic mesenchymal cell activation, leading to reduced fibrosis and preservation of renal function across preclinical CKD models. These findings support PDGF-B/D dual inhibition as a differentiated, disease-modifying therapeutic strategy for broad CKD indications.
Acknowledgment
We thank colleagues for their contributions to antibody engineering, preclinical studies, and overall research and project management.